Bladder Cancer Drug Receives FDA Approval Based on Research Led by NYU Langone

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May 19, 2017 (12:45PM)

The United States Food and Drug Administration (FDA) has granted accelerated approval to a second drug in less than a month for first-line treatment for advanced bladder cancer—again based on clinical trial findings from the same researcher from NYU Langone’s Perlmutter Cancer Center.

In a study led by medical oncologist Arjun Balar, MD, the newly approved drug, pembrolizumab, marketed under the brand name Keytruda®, was shown to harness the immune system to shrink tumors in bladder cancer patients who could not tolerate the most effective chemotherapy, offering hope to individuals with advanced disease. These findings were first presented by Dr. Balar last October at the annual meeting of the European Society for Medical Oncology and followed by an updated analysis in February at the Genitourinary Cancers Symposium.

In addition to frontline treatment, the FDA also approved pembrolizumab for patients with locally advanced or metastatic bladder cancer who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant chemotherapy treatment.

“It is extremely encouraging for those of us who study and treat bladder cancer to know that we now have a more robust set of FDA-approved options to aggressively combat this very serious disease,” Dr. Balar says. “Approval of pembrolizumab underscores the prominent role of clinical research at Perlmutter Cancer Center.”

Dr. Balar’s study found that injections of pembrolizumab shrank tumors by at least one third in 24 percent of study participants. Of those, five percent saw their tumor lesions disappear. All patients in the study were unable to take the current standard of care, cisplatin, which is a chemotherapy that prevents tumor cells from repairing damage to their DNA. More than half of people with bladder cancer, most of them elderly and ill, cannot take cisplatin because of its toxic effects on nerves, hearing, and kidneys.

“While five percent of patients who saw complete remission may seem like a small number, it’s important to note that these patients would otherwise have no approved first-line treatment option and on average die within ten months,” says Dr. Balar, an assistant professor in the Department of Medicine and director of the Genitourinary Medical Oncology Program at Perlmutter Cancer Center.

About 76,000 Americans were diagnosed with bladder cancer in 2016, with men 3 times more likely than women to develop the disease.

Treatment Is Easier on Patients

While 62 percent of participants in the study experienced side effects linked to pembrolizumab treatment, most were tolerable, including fatigue (17 percent) along with itchy skin and diarrhea. Five percent of patients in the study stopped therapy because of side effect severity.

When compared to chemotherapy, the side effect profile of pembrolizumab was “far less severe,” Dr. Balar says. In addition, among patients who achieved a response, 83 percent were ongoing at a median follow up at 5 months, while responses to most chemotherapies are temporary, he says.

Checkpoint inhibitors focus on activating the immune system, which is designed to attack foreign organisms like bacteria, while leaving the body’s healthy cells alone. To spare normal cells from immune attack, the system uses “checkpoints,” or sensors on immune cells that turn them off when they receive the right signal. The body recognizes tumors as abnormal, but cancer cells hijack checkpoints to turn off immune responses. Among the most important checkpoints is a protein called programmed death receptor 1 (PD1), which is shut down by pembrolizumab to make tumors “visible” again to the immune system.

Past studies have found that levels of programmed death receptor ligand 1 (PD-L1), the signaling partner of PD-1, vary dramatically across people with bladder cancer. Higher levels of PD-L1 are associated with higher likelihood of response, however responses are also seen in people with low or absent levels, frustrating efforts to arrive at a consensus threshold for when doctors should prescribe—or not prescribe—pembrolizumab or a similar agent in this class.

The study was supported by Merck Sharp and Dohme Corp., a subsidiary of Merck and Co., Inc. Dr. Balar is a paid consultant to Merck, the manufacturer of study drug, and the company that funded the study. The terms of these arrangements are managed in accordance with NYU Langone policies.